A distinct gastrointestinal symptom profile characterizes clinically relevant fatigue in systemic sclerosis
10 affiliations
- 1Department of Internal Medicine, University Hospital Careggi, Florence, Italy
- 2Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- 3Department of Internal Medicine, Division of Rheumatology, UTHealth Houston, Houston, TX USA
- 4Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Inflammation, Fibrosis and Ageing initiative (INFLAGE) IRCCS San Raffaele Scientific Institute, Milan, Italy
- 5Vita-Salute San Raffaele University, Milan, Italy
- 6Inflammation Fibrosis and Ageing Initiative, (INFLAGE), Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
- 7Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- 8Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
- 9Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organisation, Salford, UK
- 10NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK
Abstract
Objective: To identify the specific gastrointestinal (GI) symptoms associated with clinically relevant fatigue in systemic sclerosis (SSc), beyond the established association between overall GI involvement and fatigue.
Methods: We conducted a cross-sectional study including consecutive patients with SSc fulfilling the 2013 ACR/EULAR classification criteria. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scale, with clinically relevant fatigue defined as a score ≤ 30. Demographic, clinical, laboratory, and organ involvement data were collected. Individual GI symptom domains (GERD, dysphagia, bloating, diarrhea and constipation), together with the Medsger GI severity score, were analyzed. Bivariate analyses and multivariable logistic regression analyses were performed to evaluate symptom-specific associations with clinically relevant fatigue.
Results: Among 115 patients, clinically relevant fatigue was observed in 42 (36.5%). Patients with FACIT-Fatigue ≤ 30 more frequently reported GERD (90.5% vs 60.3%), dysphagia (40.5% vs 16.4%), bloating (66.7% vs 15.1%), and diarrhea (28.6% vs 11.0%) (all p < 0.05). No statistically significant between-group differences were detected in the available objective disease measures. In the primary Firth penalized logistic regression model, bloating (OR 9.11, 95% CI 3.53–25.71) and GERD (OR 4.08, 95% CI 1.29–15.44) were associated with clinically relevant fatigue. Dysphagia showed a directionally consistent but less precise association. In a continuous-outcome sensitivity analysis, GERD, dysphagia, and bloating were associated with lower FACIT-Fatigue scores.
Conclusions: Clinically relevant fatigue in SSc was associated with a distinct profile of patient-reported GI symptoms, particularly bloating and GERD. These findings provide a more granular characterization of fatigue-related GI burden in SSc.
Key Points
• This study moves beyond aggregate gastrointestinal involvement by examining symptom-specific correlates of fatigue in systemic sclerosis.
• Bloating and GERD were independently associated with FACIT-Fatigue ≤ 30, whereas dysphagia was associated with greater fatigue severity only in the continuous-outcome sensitivity analysis.
• Clinically relevant fatigue in SSc appears to cluster more closely with patient-reported GI and functional burden than with conventional measures of disease severity.
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BibTeX
@article{bonomi2026distinct,
title = {{A distinct gastrointestinal symptom profile characterizes clinically relevant fatigue in systemic sclerosis}},
author = {Francesco Bonomi and Silvia Peretti and Giulia Bandini and Veronica De Silvestri and Cristiano Barbetta and Ilenia Mallia and Khadija El Aoufy and Ginevra Fiori and Serena Guiducci and Alberto Moggi Pignone and Zsuzsanna H. McMahan and Marco Matucci-Cerinic and Cosimo Bruni and Michael Hughes and Silvia Bellando Randone},
journal = {Clinical Rheumatology},
year = {2026},
month = sep,
doi = {10.1007/s10067-026-08361-y},
url = {https://doi.org/10.1007/s10067-026-08361-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A distinct gastrointestinal symptom profile characterizes clinically relevant fatigue in systemic sclerosis
AU - Francesco Bonomi
AU - Silvia Peretti
AU - Giulia Bandini
AU - Veronica De Silvestri
AU - Cristiano Barbetta
AU - Ilenia Mallia
AU - Khadija El Aoufy
AU - Ginevra Fiori
AU - Serena Guiducci
AU - Alberto Moggi Pignone
AU - Zsuzsanna H. McMahan
AU - Marco Matucci-Cerinic
AU - Cosimo Bruni
AU - Michael Hughes
AU - Silvia Bellando Randone
PY - 2026
DA - 2026/09/08
JO - Clinical Rheumatology
DO - 10.1007/s10067-026-08361-y
UR - https://doi.org/10.1007/s10067-026-08361-y
AB - Objective: To identify the specific gastrointestinal (GI) symptoms associated with clinically relevant fatigue in systemic sclerosis (SSc), beyond the established association between overall GI involvement and fatigue. Methods: We conducted a cross-sectional study including consecutive patients with SSc fulfilling the 2013 ACR/EULAR classification criteria. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scale, with clinically relevant fatigue defined as a score ≤ 30. Demographic, clinical, laboratory, and organ involvement data were collected. Individual GI symptom domains (GERD, dysphagia, bloating, diarrhea and constipation), together with the Medsger GI severity score, were analyzed. Bivariate analyses and multivariable logistic regression analyses were performed to evaluate symptom-specific associations with clinically relevant fatigue. Results: Among 115 patients, clinically relevant fatigue was observed in 42 (36.5%). Patients with FACIT-Fatigue ≤ 30 more frequently reported GERD (90.5% vs 60.3%), dysphagia (40.5% vs 16.4%), bloating (66.7% vs 15.1%), and diarrhea (28.6% vs 11.0%) (all p < 0.05). No statistically significant between-group differences were detected in the available objective disease measures. In the primary Firth penalized logistic regression model, bloating (OR 9.11, 95% CI 3.53–25.71) and GERD (OR 4.08, 95% CI 1.29–15.44) were associated with clinically relevant fatigue. Dysphagia showed a directionally consistent but less precise association. In a continuous-outcome sensitivity analysis, GERD, dysphagia, and bloating were associated with lower FACIT-Fatigue scores. Conclusions: Clinically relevant fatigue in SSc was associated with a distinct profile of patient-reported GI symptoms, particularly bloating and GERD. These findings provide a more granular characterization of fatigue-related GI burden in SSc. Key Points • This study moves beyond aggregate gastrointestinal involvement by examining symptom-specific correlates of fatigue in systemic sclerosis. • Bloating and GERD were independently associated with FACIT-Fatigue ≤ 30, whereas dysphagia was associated with greater fatigue severity only in the continuous-outcome sensitivity analysis. • Clinically relevant fatigue in SSc appears to cluster more closely with patient-reported GI and functional burden than with conventional measures of disease severity.
SN - 0770-3198
SN - 1434-9949
ER -